Nerve conduction block using high frequency alternating currents (HFAC) could be useful in controlling muscle spasticity, blocking pain, or blocking unwanted activity in the autonomic nervous system. We have found that HFAC in the range of 5-40kHz can produce an immediate arrest of action potential conduction and is immediately reversible when the block is turned off. Our overall goal is to complete the steps necessary to move HFAC block into human feasibility testing. However, there remains one important impediment to the use of HFAC block for many clinical conditions; specifically, when HFAC is initiated it produces a brief but intense burst of firing in the nerve, which has been termed the onset response. This can be a significant obstacle to the clinical implementation of HFAC block because this activity will produce unwanted motor activity and will produce an intense pain sensation. It may be possible to create a no- onset nerve conduction block system that could have significant clinical application in the modulation of muscle spasticity and treatment for chronic pain. Such a system requires the development of a safe method for delivering low duty-cycle DC. Based on our preliminary work, a novel concept in electrode design, which we refer to as the Separated-Interface Nerve Electrode (SINE), may provide the solution. We propose to build upon our preliminary work and develop an electrode that is practical to implement, efficacious for nerve conduction block, and safe and durable for long term chronic use. The project consists of three Specific Aims. First we will create a practical and durable SINE electrode through evaluation of all material aspects of the SINE in order to develop an electrode design that safely produces the desired effect on the nerve. These electrodes will then be evaluated for durability through in vitro studies to evaluate electrode impedance and the capacity to transmit sufficient charge without degradation of the electrode materials. Acute in vivo studies will be performed on the rat sciatic nerve to evaluate the effectiveness of the SINE in producing a DC nerve conduction block that can be maintained for ten or more seconds without damage to the nerve. Once effective DC block has been established utilizing the SINE, combined DC and HFAC block will be tested for effectiveness in producing instantly reversible nerve block without an onset response. Finally, SINEs will be implanted on the sciatic nerve of rats for a period of six weeks. Low duty- cycle DC will be delivered through the SINE at the parameters that will be utilized for various clinical applications. Chronically blocked nerves will be examined for reaction to the DC, and electrode characteristics will be evaluated to measure durability. At the completion of this study, we will have the necessary components to develop a no-onset nerve conduction block system, allowing us to proceed with the clinical application of this method for treatment of muscle spasticity, chronic pain, and related conditions. PUBLIC HEALTH RELEVANCE: One alternative for treatment of chronic pain and muscle spasticity is to prevent nerve signals from propagating to the brain or muscle. In this project, we are developing a method of blocking nerve conduction using a combination of high frequency and direct current electrodes. The specific aim of this project is to develop an electrode that is capable of delivering low duty- cycle direct current for long-term applications.